In line for immortality

Abstract

By inhibiting the immortalization of yeast cells, scientists at Harvard Medical School (Cambridge, MA, USA) might have uncovered a novel strategy for treating cancer. Tumour cells are characterized by their infinite proliferative ability, which gives rise to immortal cell lines. In most tumour cells, this property can be attained by reactivating a gene for telomerase (EST2), enabling the cell to make telomeres and thus escape cell aging and death. In about ten percent of tumours, instead of telomerase, a telomere-stabilizing protein, WRN, is involved. In Saccharomyces cerevisiae, this protein is a RecQ-like DNA helicase encoded by the SGS1 gene. In humans, WRN is implicated in genetic-instability disorders such as Bloom syndrome, Rothmund–Thomson syndrome and Werner syndrome. When comparing yeast cells lacking both telomerase and WRN, with cells lacking just telomerase, David Sinclair and Haim Cohen, pathologists from Harvard, found that the former senesce more rapidly, experience a higher rate of telomere erosion, and exhibit delayed and only partial recovery from senescence [Proc. Natl. Acad. Sci. U. S. A. 98, 3174–3179]. The cells lacking only telomerase acquired immortality by using the WRN protein. Blocking telomerase alone has not been successful as an anti-cancer therapeutic strategy because cells can switch to the alternative WRN pathway. ‘So we have to have a double-pronged attack’, said Sinclair, ‘if we could block or inhibit the WRN protein in these ten percent of cancers [those using WRN to become immortal], we'd have a good chance of preventing proliferation’. S de B